Major hemorrhage on anticoagulants is a dramatic presentation that creates a bias against restarting the anticoagulant for fear of precipitating another hemorrhage. What often gets lost in this one-sided assessment of risk is the underlying threat of thromboembolic disease, for which the patient was anticoagulated to begin with. A more balanced approach between the risk of hemorrhage and stroke and prospective randomized data on which to base it is direly needed. This proposal is relevant to the mission of NHLBI as it deals with heart disease, since the most common indication for oral anticoagulation is atrial fibrillation. It deals with blood disease, albeit an iatrogenic coagulopathy caused by anticoagulation therapy. It deals with the clinical setting of bleeding, both in gastrointestinal bleeding and intracranial hemorrhage. It aims to enhance the health of patients with these diseases by studying the risk/benefit of restarting anticoagulation after major hemorrhage. Its goals are immediately translational into clinical practice. It fosters training and mentoring of an emerging scientist and physician, and it creates and supports a robust, collaborative research infrastructure in partnership with the private non-profit Seton Healthcare Family and the new University of Texas Dell Medical School in Austin. There are no evidence-based guidelines on when to restart warfarin after major hemorrhage, much less the Novel Oral Anticoagulants (NOACs) increasingly being used. The overall goal of this application is to elucidate a research plan to inform the clinical decision to restart anticoagulation after major hemorrhage that will establish Dr. Milling as an independent impactful researcher in this field. Dr. Milling will enrollin a formal master's degree program: Masters of Science in Clinical Investigations at the University of Texas Health Science Center - San Antonio. He will also undergo extensive and immersive training in hemostasis and coagulation, the design and conduct of multicenter clinical trials, conceptual training in the field of adaptive trial design, and health economics. Dr. Milling will receive careful mentorship from Drs. Steven Warach, Scott Berry Todd Olmstead and Jerrold Levy utilizing both formal training curriculum and informal meeting frameworks to draw from their extensive and diverse experience and guidance. Dr. Milling will conduct a three-phased research design, including the development of a National Practice Survey Tool for Clinical Trials (survey of patients, PCPs, and Cardiologists), laying the ground work for a larger multicenter, adaptive, time dose clinical trial and a future R01 submission, to find the ideal time to restart oral anticoagulants after a major hemorrhage that balances the risk of recurrent hemorrhage with the risk of thromboembolic disease.